Amorphous vortioxetine and salts thereof

Abstract

The present invention relates to an amorphous vortioxetine and salts thereof. In particular, the invention relates to a process for the preparation of an amorphous vortioxetine hydrobromide. Further, the invention also relates to a process for preparation of amorphous vortioxetine free base. The invention also relates to pharmaceutical compositions comprising an amorphous vortioxetine or hydrobromide salt thereof for oral administration for treatment of major depressive disorder (MDD) and generalized anxiety disorder (GAD).

We claim: 
     
       1. Amorphous vortioxetine hydrobromide of Formula (II) having a purity by HPLC of greater than 98%, 
       
         
           
           
               
               
           
         
       
     
     
       2. A stable amorphous vortioxetine hydrobromide that does not convert to any other solid form and contains less than 0.5% (wt/wt) total impurities when stored at a temperature of up to about 40° C. and at a relative humidity of about 25% to about 75% for about three months. 
     
     
       3. The amorphous vortioxetine hydrobromide according to  claim 1  having a residual solvent less than 0.5%. 
     
     
       4. A solid dispersion of amorphous vortioxetine free base or salts thereof having a purity by HPLC of more than 98% and a polymer. 
     
     
       5. The solid dispersion according to  claim 4 , wherein the polymer is a non-ionic polymer or an ionic polymer. 
     
     
       6. The solid dispersion according to  claim 5 , wherein the polymer comprises one or more of hydroxypropylmethyl cellulose acetate succinate, hydroxypropylmethyl cellulose, methacrylic acid copolymers, and polyvinyl pyrrolidone. 
     
     
       7. The solid dispersion according to  claim 4 , wherein the salt is a hydrobromide salt. 
     
     
       8. The solid dispersion according to  claim 4  substantially free from residual solvents. 
     
     
       9. A pharmaceutical composition comprising amorphous vortioxetine hydrobromide having purity by HPLC of more than 98% together with one or more pharmaceutically acceptable carriers, excipients or diluents. 
     
     
       10. A pharmaceutical composition comprising a solid dispersion of amorphous vortioxetine hydrobromide having purity by HPLC of more than 98% and a polymer together with one or more of pharmaceutically acceptable carriers, excipients or diluents. 
     
     
       11. The amorphous vortioxetine hydrobromide according to  claim 1 , having particle size distributions,
 D(10) of about 50 μm or less, D(50) of about 200 μm or less, and D(90) of about 400 μm or less; or 
 D(10) of about 25 μm or less, D(50) of about 100 μm or less and D(90) of about 250 μm or less. 
 
     
     
       12. A pharmaceutical composition comprising the amorphous vortioxetine hydrobromide according to  claim 1 , having particle size distributions,
 D(10) of about 50 μm or less, D(50) of about 200 μm or less and D(90) of about 400 μm or less; or 
 D(10) of about 25 μm or less, D(50) of about 100 μm or less and D(90) of about 250 μm or less together with one or more of pharmaceutically acceptable carriers, excipients or diluents. 
 
     
     
       13. The amorphous vortioxetine hydrobromide according to  claim 1 , having particle size distribution, D(10) of about 50 μm or less, D(50) of about 200 μm or less and D(90) of about 400 μm or less.